PMC:7455777 / 7704-9191 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7455777","sourcedb":"PMC","sourceid":"7455777","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7455777","text":"Viral infection is often associated with cell death, and numerous molecular pathways have been proposed to explain the neurovirulence of HCoVs [10]. For example, parthanatos, caspase independent-apoptosis and programmed necrosis pathways may be involved in the neuropathogenesis of HCoV-OC43. These molecular pathways can also interact with one other by sharing the same cellular factors (such as calcium overload, mitochondrial dysfunction or endoplasmic reticulum stress, excitatory amino acid toxicity), and active compounds (such as reactive oxygen species) (Fig. 1). However, it remains to be determined whether and how SARS-CoV-2 affects the function of CNS cells.\nFig. 1 HCoVs probably exhibit neuropathological consequences through multiple routes. ① Direct invasion. After invasion, the production and release of virus may induce cell death by several pathways. ② Immune response. The virus can lead to over-activation of host immune response, releasing a large number of pro-inflammatory cytokines and chemokines (e.g., IL-6, IL-1β, IL-2, IL-8, IL-17, G-CSF, GM-CSF, IP10, MCP1, CCL3, and TNF). Cytokine signal pathways will subsequently induce the cell death and tissue damage. ③ Neuroendocrine-immune crosstalk. Aberrant release of neuropeptides from the infected neurons may act at the endocrine glands, such as adrenal gland. These neuropeptides might cause anomalous release of glucocorticoids and other peptides, which may contribute to the dysregulation of immune 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